Using total plasma triacylglycerol to assess hepatic de novo lipogenesis as an alternative to VLDL triacylglycerol

Abstract

Background: Hepatic de novo lipogenesis (DNL) is ideally measured in very low-density lipoprotein (VLDL)-triacylglycerol (TAG). In the fasting state, the majority of plasma TAG typically represents VLDL-TAG; however, the merits of measuring DNL in total plasma TAG have not been assessed. This study aimed to assess the performance of DNL measured in VLDL-TAG (DNL_VLDL-TAG) compared to that measured in total plasma TAG (DNL_Plasma-TAG).

Methods: Using deuterated water, newly synthesised palmitate was determined in fasting plasma VLDL-TAG and total TAG in 63 subjects taking part in multiple studies resulting in n = 123 assessments of DNL (%new palmitate of total palmitate). Subjects were split into tertiles to investigate if DNL_Plasma-TAG could correctly classify subjects having ‘high’ (top tertile) and ‘low’ (bottom tertile) DNL. Repeatability was assessed in a subgroup (n = 16) with repeat visits.

Results: DNL_VLDL-TAG was 6.8% (IQR 3.6–10.7%) and DNL_Plasma-TAG was 7.5% (IQR 4.0%−11.0%), and the correlation between the methods was r_s = 0.62 (p < 0.0001). Bland–Altman plots demonstrated similar performance (mean difference 0.81%, p = 0.09); however, the agreement interval was wide (−9.6% to 11.2%). Compared to DNL_VLDL-TAG, 54% of subjects with low DNL were correctly classified, whilst 66% of subjects with high DNL were correctly classified using DNL_Plasma-TAG. Repeatability was acceptable (i.e. not different) at the group level, but the majority of subjects had an intra-individual variability over 25%.

Conclusion: DNL in total plasma TAG performed similarly to DNL in VLDL-TAG at the group level, but there was large variability at the individual level. We suggest that plasma TAG could be useful for comparing DNL between groups.

Keywords:

• De novo lipogenesis
• DNL
• hepatic
• human
• triacylglycerol
• VLDL

Acknowledgements

Authors thank Louise Dennis, Rachel Craven-Todd, and CRU staff for excellent nursing provision, and Niall Dempster and Jonathan Hazlehurst for medical cover. This work was supported by the NIHR Biomedical Research Centre, Oxford, and Authors thank the volunteers from the Oxford Biobank, NIHR Oxford Biomedical Research Centre, for their participation. The Oxford Biobank (www.oxfordbiobank.org.uk) is also part of the NIHR National Bioresource which supported the recalling process of the volunteers. A small number of samples analysed in this paper were from CJG’s Novo Nordisk postdoctoral fellowship run in partnership with the University of Oxford.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

FR is supported by Henning and Johan Throne-Holsts Foundation, Swedish Society for Medical Research, Swedish Society of Medicine, and The Foundation Blanceflor. LH is a British Heart Foundation Senior Research Fellow in Basic Science (FS/15/56/31645).

Notes on contributors

Leanne Hodson

Leanne Hodson, PhD is a professor of metabolic physiology at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, United Kingdom.

Sion A. Parry

Sion A. Parry, PhD is a researcher at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, United Kingdom.

Thomas Cornfield

Thomas Cornfield, BSc is a research technician at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, United Kingdom.

Catriona Charlton

Catriona Charlton, BSc was a research technician at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, United Kingdom at the time of the work, now a laboratory analyst at Essentra Laboratories.

Wee Suan Low

Wee Suan Low, PhD was a doctoral student at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, United Kingdom at the time of the work, now a research fellow at A*STAR – Agency for Science, Technology and Research, Singapore.

Charlotte J. Green

Charlotte J. Green, PhD was a researcher at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, United Kingdom at the time of the work, now a Scientific Liaison Manager at the University of Dundee, United Kingdom.

Fredrik Rosqvist

Fredrik Rosqvist, PhD was a postdoctoral researcher at the Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, United Kingdom at the time of the work, now a researcher at the Department of public health and caring sciences, Clinical nutrition and metabolism, Uppsala University, Sweden.